{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,16]],"date-time":"2026-03-16T13:12:11Z","timestamp":1773666731851,"version":"3.50.1"},"reference-count":124,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2021,7,30]],"date-time":"2021-07-30T00:00:00Z","timestamp":1627603200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Neurol."],"abstract":"<jats:p>The new coronavirus disease COVID-19 was identified in December 2019. It subsequently spread across the world with over 125 M reported cases and 2.75 M deaths in 190 countries. COVID-19 causes severe respiratory distress; however, recent studies have reported neurological consequences of infection by the COVID-19 virus SARS-CoV-2 even in subjects with mild infection and no initial neurological effects. It is likely that the virus uses the olfactory nerve to reach the CNS and that this transport mechanism enables virus access to areas of the brain stem that regulates respiratory rhythm and may even trigger cell death by alteration of these neuronal nuclei. In addition, the long-term neuronal effects of COVID-19 suggest a role for SARS-CoV-2 in the development or progression of neurodegerative disease as a result of inflammation and\/or hypercoagulation. In this review recent findings on the mechanism(s) by which SARS-CoV-2 accesses the CNS and induces neurological dysregulation are summarized.<\/jats:p>","DOI":"10.3389\/fneur.2021.697079","type":"journal-article","created":{"date-parts":[[2021,7,30]],"date-time":"2021-07-30T06:02:28Z","timestamp":1627624948000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":14,"title":["The Immunopathogenesis of Neuroinvasive Lesions of SARS-CoV-2 Infection in COVID-19 Patients"],"prefix":"10.3389","volume":"12","author":[{"given":"Shamila D.","family":"Alipoor","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Esmaeil","family":"Mortaz","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mohammad","family":"Varahram","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Johan","family":"Garssen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ian M.","family":"Adcock","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2021,7,30]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/j.bbi.2016.03.010","article-title":"The blood-brain barrier in systemic inflammation","volume":"60","author":"Varatharaj","year":"2017","journal-title":"Brain Behav Immun."},{"key":"B2","doi-asserted-by":"publisher","first-page":"2064","DOI":"10.1016\/j.neurobiolaging.2013.02.010","article-title":"Increased blood-brain barrier vulnerability to systemic inflammation in an Alzheimer disease mouse model","volume":"34","author":"Takeda","year":"2013","journal-title":"Neurobiol Aging."},{"key":"B3","doi-asserted-by":"publisher","first-page":"18","DOI":"10.1016\/j.bbi.2020.03.031","article-title":"Nervous system involvement after infection with COVID-19 and other coronaviruses","volume":"87","author":"Wu","year":"2020","journal-title":"Brain Behav Immun"},{"key":"B4","doi-asserted-by":"publisher","first-page":"73","DOI":"10.1146\/annurev-immunol-042718-041417","article-title":"Neuroinflammation during RNA viral infections","volume":"37","author":"Klein","year":"2019","journal-title":"Annu Rev Immunol."},{"key":"B5","doi-asserted-by":"publisher","first-page":"1089","DOI":"10.1086\/444461","article-title":"Detection of severe acute respiratory syndrome coronavirus in the brain: potential role of the chemokine mig in pathogenesis","volume":"41","author":"Xu","year":"2005","journal-title":"Clin Infect Dis."},{"key":"B6","doi-asserted-by":"publisher","first-page":"2108","DOI":"10.1373\/clinchem.2003.025437","article-title":"Detection of SARS coronavirus RNA in the cerebrospinal fluid of a patient with severe acute respiratory syndrome","volume":"49","author":"Hung","year":"2003","journal-title":"Clin Chem."},{"key":"B7","doi-asserted-by":"publisher","first-page":"415","DOI":"10.1084\/jem.20050828","article-title":"Multiple organ infection and the pathogenesis of SARS","volume":"202","author":"Gu","year":"2005","journal-title":"J Exp Med."},{"key":"B8","doi-asserted-by":"publisher","first-page":"7264","DOI":"10.1128\/JVI.00737-08","article-title":"Severe acute respiratory syndrome coronavirus infection causes neuronal death in the absence of encephalitis in mice transgenic for human ACE2","volume":"82","author":"Netland","year":"2008","journal-title":"J Virol."},{"key":"B9","doi-asserted-by":"publisher","first-page":"502","DOI":"10.1016\/0042-6822(92)90220-J","article-title":"Human coronavirus gene expression in the brains of multiple sclerosis patients","volume":"191","author":"Stewart","year":"1992","journal-title":"Virology."},{"key":"B10","doi-asserted-by":"publisher","first-page":"382","DOI":"10.1128\/CMR.6.4.382","article-title":"Epidemiologic evidence for multiple sclerosis as an infection","volume":"6","author":"Kurtzke","year":"1993","journal-title":"Clin Microbiol Rev."},{"key":"B11","doi-asserted-by":"publisher","first-page":"335","DOI":"10.1016\/j.virol.2006.01.049","article-title":"Human coronavirus OC43 infection induces chronic encephalitis leading to disabilities in BALB\/C mice","volume":"349","author":"Jacomy","year":"2006","journal-title":"Virology."},{"key":"B12","doi-asserted-by":"publisher","first-page":"1329","DOI":"10.1007\/s10072-020-04469-4","article-title":"Potential neurological impact of coronaviruses: implications for the novel SARS-CoV-2","volume":"41","author":"Iroegbu","year":"2020","journal-title":"Neurol Sci."},{"key":"B13","first-page":"1372","article-title":"Immunofluorescence studies on the pathogenesis of hemagglutinating encephalomyelitis virus infection in pigs after oronasal inoculation","volume":"41","author":"Andries","year":"1980","journal-title":"Am J Vet Res."},{"key":"B14","doi-asserted-by":"publisher","first-page":"e00404","DOI":"10.1128\/JVI.00404-18","article-title":"Axonal transport enables neuron-to-neuron propagation of human coronavirus OC43","volume":"92","author":"Dub\u00e9","year":"2018","journal-title":"J Virol."},{"key":"B15","doi-asserted-by":"publisher","first-page":"659","DOI":"10.3389\/fneur.2020.00659","article-title":"Potential of SARS-CoV-2 to cause CNS infection: biologic fundamental and clinical experience","volume":"11","author":"Huang","year":"2020","journal-title":"Front Neurol."},{"key":"B16","doi-asserted-by":"publisher","first-page":"1104","DOI":"10.1002\/mds.28179","article-title":"SARS-CoV2 as a potential trigger of neurodegenerative diseases","volume":"35","author":"Gomez-Pinedo","year":"2020","journal-title":"Mov Disord"},{"key":"B17","doi-asserted-by":"publisher","first-page":"eabc5801","DOI":"10.1126\/sciadv.abc5801","article-title":"Non-neuronal expression of SARS-CoV-2 entry genes in the olfactory system suggests mechanisms underlying COVID-19-associated anosmia","volume":"6","author":"Brann","year":"2020","journal-title":"Sci Adv."},{"key":"B18","doi-asserted-by":"publisher","first-page":"338","DOI":"10.4149\/av_2015_04_338","article-title":"Transolfactory neuroinvasion by viruses threatens the human brain","volume":"59","author":"Mori","year":"2015","journal-title":"Acta Virol."},{"key":"B19","doi-asserted-by":"publisher","first-page":"14","DOI":"10.3390\/v12010014","article-title":"Human coronaviruses and other respiratory viruses: underestimated opportunistic pathogens of the central nervous system?","volume":"12","author":"Desforges","year":"2019","journal-title":"Viruses."},{"key":"B20","doi-asserted-by":"publisher","first-page":"995","DOI":"10.1021\/acschemneuro.0c00122","article-title":"Evidence of the COVID-19 virus targeting the CNS: tissue distribution, host-virus interaction, and proposed neurotropic mechanisms","volume":"11","author":"Baig","year":"2020","journal-title":"ACS Chem Neurosci."},{"key":"B21","doi-asserted-by":"publisher","first-page":"856","DOI":"10.1126\/science.abd2985","article-title":"Neuropilin-1 facilitates SARS-CoV-2 cell entry and infectivity","volume":"370","author":"Cantuti-Castelvetri","year":"2020","journal-title":"Science."},{"key":"B22","doi-asserted-by":"publisher","first-page":"825","DOI":"10.1016\/j.apsb.2018.06.006","article-title":"Efficacy of inverso isomer of CendR peptide on tumor tissue penetration","volume":"8","author":"Wang","year":"2018","journal-title":"Acta Pharmaceutica Sinica B."},{"key":"B23","doi-asserted-by":"publisher","first-page":"4221","DOI":"10.3892\/mmr.2020.11510","article-title":"Neuropilin 1 as a new potential SARS-CoV 2 infection mediator implicated in the neurologic features and central nervous system involvement of COVID-19","volume":"22","author":"Davies","year":"2020","journal-title":"Mol Med Rep."},{"key":"B24","doi-asserted-by":"publisher","first-page":"563085","DOI":"10.3389\/fcimb.2021.563085","article-title":"COVID-19: molecular and cellular response","volume":"11","author":"Alipoor","year":"2021","journal-title":"Front Cell Infect Microbiol."},{"key":"B25","doi-asserted-by":"publisher","first-page":"861","DOI":"10.1126\/science.abd3072","article-title":"Neuropilin-1 is a host factor for SARS-CoV-2 infection","volume":"370","author":"Daly","year":"2020","journal-title":"Science."},{"key":"B26","doi-asserted-by":"publisher","first-page":"919","DOI":"10.1016\/S1474-4422(20)30308-2","article-title":"Neuropathology of patients with COVID-19 in Germany: a post-mortem case series","volume":"19","author":"Matschke","year":"2020","journal-title":"Lancet Neurol."},{"key":"B27","doi-asserted-by":"publisher","first-page":"16","DOI":"10.4149\/av_2018_102","article-title":"Disruption of the blood brain barrier is vital property of neurotropic viral infection of the central nervous system","volume":"62","author":"Al-Obaidi","year":"2018","journal-title":"Acta Virol."},{"key":"B28","doi-asserted-by":"publisher","first-page":"52","DOI":"10.3389\/fcimb.2019.00052","article-title":"Brain infection by hepatitis E virus probably via damage of the blood-brain barrier due to alterations of tight junction proteins","volume":"9","author":"Tian","year":"2019","journal-title":"Front Cell Infect Microbiol."},{"key":"B29","doi-asserted-by":"publisher","first-page":"e02731","DOI":"10.1128\/mBio.02731-19","article-title":"Encephalitic alphaviruses exploit caveola-mediated transcytosis at the blood-brain barrier for central nervous system entry","volume":"11","author":"Salimi","year":"2020","journal-title":"Mbio"},{"key":"B30","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1007\/s10787-021-00806-x.","article-title":"Neuropathophysiology of coronavirus disease 2019: neuroinflammation and blood brain barrier disruption are critical pathophysiological processes that contribute to the clinical symptoms of SARS-CoV-2 infection","author":"Welcome","year":"2021","journal-title":"Inflammopharmacology"},{"key":"B31","doi-asserted-by":"publisher","first-page":"163","DOI":"10.1097\/QAD.0b013e32833424c8","article-title":"Targeting trojan horse leukocytes for HIV prevention","volume":"24","author":"Anderson","year":"2010","journal-title":"AIDS."},{"key":"B32","doi-asserted-by":"publisher","first-page":"4430","DOI":"10.1038\/s41467-019-12408-x","article-title":"Zika virus enhances monocyte adhesion and transmigration favoring viral dissemination to neural cells","volume":"10","author":"Ayala-Nunez","year":"2019","journal-title":"Nat Commun."},{"key":"B33","doi-asserted-by":"publisher","first-page":"2158","DOI":"10.3389\/fmicb.2019.02158","article-title":"Selective disruption of the blood-brain barrier by zika virus","volume":"10","author":"Leda","year":"2019","journal-title":"Front Microbiol."},{"key":"B34","doi-asserted-by":"publisher","first-page":"351","DOI":"10.1038\/s41577-020-0317-2","article-title":"Macrophages: a Trojan horse in COVID-19?","volume":"20","author":"Park","year":"2020","journal-title":"Nat Rev Immunol."},{"key":"B35","doi-asserted-by":"publisher","first-page":"368","DOI":"10.1038\/s41593-020-00771-8","article-title":"The S1 protein of SARS-CoV-2 crosses the blood\u2013brain barrier in mice","volume":"24","author":"Rhea","year":"2021","journal-title":"Nat Neurosci."},{"key":"B36","doi-asserted-by":"publisher","first-page":"533","DOI":"10.1016\/S2213-2600(21)00125-9","article-title":"Confronting COVID-19-associated cough and the post-COVID syndrome: role of viral neurotropism, neuroinflammation, neuroimmune responses","volume":"9","author":"Woo-Jung Song","year":"2021","journal-title":"Lancet Respir Med."},{"key":"B37","doi-asserted-by":"publisher","first-page":"91","DOI":"10.3390\/diagnostics9030091","article-title":"Myalgic encephalomyelitis\/chronic fatigue syndrome: a comprehensive review","volume":"9","author":"Cortes Rivera","year":"2019","journal-title":"Diagnostics."},{"key":"B38","doi-asserted-by":"publisher","first-page":"117179","DOI":"10.1016\/j.jns.2020.117179","article-title":"Post-COVID 19 Neurological Syndrome (PCNS); a novel syndrome with challenges for the global neurology community","volume":"419","author":"Wijeratne","year":"2020","journal-title":"J Neurol Sci."},{"key":"B39","doi-asserted-by":"publisher","first-page":"e13746","DOI":"10.1111\/ijcp.13746","article-title":"Assessment and characterisation of post-COVID-19 manifestations","volume":"75","author":"Kamal","year":"2021","journal-title":"Int J Clin Pract."},{"key":"B40","doi-asserted-by":"publisher","first-page":"e4","DOI":"10.1016\/j.jinf.2020.08.029","article-title":"Post-discharge persistent symptoms and health-related quality of life after hospitalization for COVID-19","volume":"81","author":"Garrigues","year":"2020","journal-title":"J Infect."},{"key":"B41","doi-asserted-by":"publisher","first-page":"1013","DOI":"10.1002\/jmv.26368","article-title":"Postdischarge symptoms and rehabilitation needs in survivors of COVID-19 infection: a cross-sectional evaluation","volume":"93","author":"Halpin","year":"2021","journal-title":"J Med Virol."},{"key":"B42","doi-asserted-by":"publisher","first-page":"135529","DOI":"10.1016\/j.neulet.2020.135529","article-title":"Neuroimaging findings in COVID-19: a narrative review","volume":"742","author":"Katal","year":"2020","journal-title":"Neurosci Lett."},{"key":"B43","doi-asserted-by":"publisher","first-page":"2823","DOI":"10.1007\/s00259-021-05215-4","article-title":"18 F-FDG brain PET hypometabolism in patients with long COVID","volume":"48","author":"Guedj","year":"2021","journal-title":"Eur J Nucl Med Mol Imaging."},{"key":"B44","doi-asserted-by":"publisher","first-page":"147329","DOI":"10.1172\/JCI147329","article-title":"Long-term micro-structure and cerebral blood flow changes in patients recovered from COVID-19 without neurological manifestations","volume":"131","author":"Qin","year":"2021","journal-title":"J Clin Investig."},{"key":"B45","doi-asserted-by":"publisher","first-page":"2494","DOI":"10.1097\/j.pain.0000000000002051","article-title":"ACE2 and SCARF expression in human dorsal root ganglion nociceptors: implications for SARS-CoV-2 virus neurological effects","volume":"161","author":"Shiers","year":"2020","journal-title":"Pain."},{"key":"B46","doi-asserted-by":"publisher","first-page":"1491","DOI":"10.1007\/s00701-020-04374-x","article-title":"SARS-CoV-2 can induce brain and spine demyelinating lesions","volume":"162","author":"Zanin","year":"2020","journal-title":"Acta Neurochir (Wien)."},{"key":"B47","doi-asserted-by":"publisher","first-page":"899","DOI":"10.3233\/JPD-202073","article-title":"COVID-19 and Parkinson's disease: are we dealing with short-term impacts or something worse?","volume":"10","author":"Victorino","year":"2020","journal-title":"J Parkinsons Dis."},{"key":"B48","doi-asserted-by":"publisher","first-page":"1099","DOI":"10.37879\/belleten.2015.1099","article-title":"The impact of the Spanish influenza on the Ottoman Empire","volume":"79","author":"Yolun","year":"2015","journal-title":"Belleten."},{"key":"B49","doi-asserted-by":"publisher","first-page":"14063","DOI":"10.1073\/pnas.0900096106","article-title":"Highly pathogenic H5N1 influenza virus can enter the central nervous system and induce neuroinflammation and neurodegeneration","volume":"106","author":"Jang","year":"2009","journal-title":"Proc Natl Acad Sci."},{"key":"B50","doi-asserted-by":"publisher","first-page":"683","DOI":"10.1001\/jamaneurol.2020.1127","article-title":"Neurologic manifestations of hospitalized patients with coronavirus disease 2019 in Wuhan, China","volume":"77","author":"Mao","year":"2020","journal-title":"JAMA Neurol."},{"key":"B51","doi-asserted-by":"publisher","first-page":"55","DOI":"10.1016\/j.ijid.2020.03.062","article-title":"A first case of meningitis\/encephalitis associated with SARS-Coronavirus-2","volume":"94","author":"Moriguchi","year":"2020","journal-title":"Int J Infect Dis."},{"key":"B52","doi-asserted-by":"publisher","first-page":"507","DOI":"10.1016\/S0140-6736(20)30211-7","article-title":"Epidemiological and clinical characteristics of 99 cases of 2019 novel coronavirus pneumonia in Wuhan, China: a descriptive study","volume":"395","author":"Chen","year":"2020","journal-title":"Lancet."},{"key":"B53","doi-asserted-by":"publisher","first-page":"565","DOI":"10.3389\/fneur.2020.00565","article-title":"Neurologic characteristics in coronavirus disease 2019 (COVID-19): a systematic review and meta-analysis","volume":"11","author":"Pinzon","year":"2020","journal-title":"Front Neurol."},{"key":"B54","doi-asserted-by":"publisher","first-page":"379","DOI":"10.1016\/j.chom.2013.03.010","article-title":"Virus infections in the nervous system","volume":"13","author":"Koyuncu","year":"2013","journal-title":"Cell Host Microbe."},{"key":"B55","doi-asserted-by":"publisher","first-page":"945","DOI":"10.1016\/j.bbi.2020.04.017","article-title":"Encephalitis as a clinical manifestation of COVID-19","volume":"88","author":"Ye","year":"2020","journal-title":"Brain Behav Immun"},{"key":"B56","doi-asserted-by":"publisher","first-page":"842","DOI":"10.1016\/j.it.2019.07.005","article-title":"Interferon control of neurotropic viral infections","volume":"40","author":"Milora","year":"2019","journal-title":"Trends Immunol."},{"key":"B57","doi-asserted-by":"publisher","first-page":"1517","DOI":"10.1016\/S0140-6736(20)30920-X","article-title":"SARS-CoV-2 and viral sepsis: observations and hypotheses","volume":"395","author":"Li","year":"2020","journal-title":"Lancet."},{"key":"B58","doi-asserted-by":"publisher","first-page":"299","DOI":"10.1016\/bs.pmbts.2019.06.002","article-title":"Can infections trigger alpha-synucleinopathies?","volume":"168","author":"Tulisiak","year":"2018","journal-title":"Prog Mol Biol Transl Sci."},{"key":"B59","doi-asserted-by":"publisher","first-page":"2767","DOI":"10.1128\/JVI.02949-15","article-title":"Alpha-synuclein expression restricts RNA viral infections in the brain","volume":"90","author":"Beatman","year":"2016","journal-title":"J Virol."},{"key":"B60","doi-asserted-by":"publisher","first-page":"719","DOI":"10.1016\/S1474-4422(20)30269-6","article-title":"COVID-19 and selective vulnerability to Parkinson's disease","volume":"19","author":"Pavel","year":"2020","journal-title":"Lancet Neurol."},{"key":"B61","doi-asserted-by":"publisher","first-page":"303","DOI":"10.1007\/s00401-016-1648-8","article-title":"Toll-like receptor 2 is increased in neurons in Parkinson's disease brain and may contribute to alpha-synuclein pathology","volume":"133","author":"Dzamko","year":"2017","journal-title":"Acta Neuropathol."},{"key":"B62","doi-asserted-by":"publisher","first-page":"4129","DOI":"10.3390\/ijms19124129","article-title":"Extracellular interactions of alpha-synuclein in multiple system atrophy","volume":"19","author":"Valdinocci","year":"2018","journal-title":"Int J Mol Sci."},{"key":"B63","doi-asserted-by":"publisher","first-page":"533","DOI":"10.1096\/fj.04-2751com","article-title":"Aggregated \u03c2\u00b1\u00e2\u20ac\u2111synuclein activates microglia: a process leading to disease progression in Parkinson's disease","volume":"19","author":"Zhang","year":"2005","journal-title":"FASEB J."},{"key":"B64","doi-asserted-by":"publisher","first-page":"193","DOI":"10.1038\/nrneurol.2010.17","article-title":"Microglia in neurodegenerative disease","volume":"6","author":"Perry","year":"2010","journal-title":"Nat Rev Neurol."},{"key":"B65","doi-asserted-by":"publisher","first-page":"350","DOI":"10.1002\/mds.26069","article-title":"Gut microbiota are related to Parkinson's disease and clinical phenotype","volume":"30","author":"Scheperjans","year":"2015","journal-title":"Mov Disord."},{"key":"B66","doi-asserted-by":"publisher","first-page":"541","DOI":"10.1016\/bs.irn.2017.05.028","article-title":"Anosmia and ageusia in parkinson's disease","volume":"133","author":"Tarakad","year":"2017","journal-title":"Int Rev Neurobiol."},{"key":"B67","doi-asserted-by":"publisher","first-page":"245","DOI":"10.1016\/j.nrleng.2020.04.002","article-title":"Impact of SARS-CoV-2 infection on neurodegenerative and neuropsychiatric diseases: a delayed pandemic?","volume":"35","author":"Serrano-Castro","year":"2020","journal-title":"Neurolog\u00eda (Engl Ed)"},{"key":"B68","doi-asserted-by":"publisher","first-page":"2020","DOI":"10.1101\/2020.03.22.002386","article-title":"A SARS-CoV-2-human protein-protein interaction map reveals drug targets and potential drug-repurposing","volume":"22","author":"Gordon","year":"2020","journal-title":"bioRxiv."},{"key":"B69","doi-asserted-by":"publisher","first-page":"39","DOI":"10.1016\/j.nbd.2015.03.014","article-title":"mTOR signaling in aging and neurodegeneration: at the crossroad between metabolism dysfunction and impairment of autophagy","volume":"84","author":"Perluigi","year":"2015","journal-title":"Neurobiol Dis."},{"key":"B70","doi-asserted-by":"publisher","first-page":"3716","DOI":"10.1172\/JCI84433","article-title":"Hypoxia-dependent regulation of inflammatory pathways in immune cells","volume":"126","author":"Taylor","year":"2016","journal-title":"J Clin Investig."},{"key":"B71","doi-asserted-by":"publisher","first-page":"397","DOI":"10.1007\/s00401-020-02190-2","article-title":"Microvascular injury and hypoxic damage: emerging neuropathological signatures in COVID-19","volume":"140","author":"Jaunmuktane","year":"2020","journal-title":"Acta Neuropathol."},{"key":"B72","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1186\/s12931-020-01530-w","article-title":"Hypoxemia in COVID-19: cerebral oximetry should be explored as a warning indicator for mechanically ventilated adults with COVID-19","volume":"21","author":"Ferrari","year":"2020","journal-title":"Respir Res."},{"key":"B73","doi-asserted-by":"publisher","first-page":"824","DOI":"10.1080\/02656736.2017.1385860","article-title":"Activation of hypoxia-inducible factor-1\u03b1 in rat brain after perinatal anoxia: role of body temperature","volume":"34","author":"Kletkiewicz","year":"2018","journal-title":"Int J Hyperthermia."},{"key":"B74","doi-asserted-by":"publisher","first-page":"L631","DOI":"10.1152\/ajplung.90415.2008","article-title":"Role of HIF-1\u03b1 in the regulation ACE and ACE2 expression in hypoxic human pulmonary artery smooth muscle cells","volume":"297","author":"Zhang","year":"2009","journal-title":"Am J Physiol Lung Cell Mol Physiol."},{"key":"B75","doi-asserted-by":"publisher","first-page":"1539","DOI":"10.1038\/s41401-020-00554-8","article-title":"Hypoxia, HIF-1\u03b1, and COVID-19: from pathogenic factors to potential therapeutic targets","volume":"41","author":"Serebrovska","year":"2020","journal-title":"Acta Pharmacol Sinica."},{"key":"B76","doi-asserted-by":"publisher","first-page":"511","DOI":"10.1159\/000445643","article-title":"HIF-1\u03b1 activation attenuates IL-6 and TNF-\u03b1 pathways in hippocampus of rats following transient global ischemia","volume":"39","author":"Xing","year":"2016","journal-title":"Cell Physiol Biochem."},{"key":"B77","doi-asserted-by":"publisher","first-page":"980","DOI":"10.12998\/wjcc.v8.i5.980","article-title":"Anomalous retinal artery associated with branch retinal artery occlusion and neovascular glaucoma: a case report","volume":"8","author":"Yang","year":"2020","journal-title":"World J Clin Cases."},{"key":"B78","doi-asserted-by":"publisher","first-page":"E119","DOI":"10.1148\/radiol.2020201187","article-title":"COVID-19\u2013associated acute hemorrhagic necrotizing encephalopathy: imaging features","volume":"296","author":"Poyiadji","year":"2020","journal-title":"Radiology."},{"key":"B79","doi-asserted-by":"publisher","first-page":"8240","DOI":"10.1523\/JNEUROSCI.1808-05.2005","article-title":"Microglial phagocytosis induced by fibrillar \u03b2-amyloid and IgGs are differentially regulated by proinflammatory cytokines","volume":"25","author":"Koenigsknecht-Talboo","year":"2005","journal-title":"J Neurosci."},{"key":"B80","doi-asserted-by":"publisher","first-page":"219","DOI":"10.1515\/revneuro-2020-0070","article-title":"CNS implications of COVID-19: a comprehensive review","volume":"32","author":"Nagu","year":"2020","journal-title":"Rev Neurosci."},{"key":"B81","doi-asserted-by":"publisher","first-page":"739","DOI":"10.1002\/ana.25197","article-title":"Inflammatory intrathecal profiles and cortical damage in multiple sclerosis","volume":"83","author":"Magliozzi","year":"2018","journal-title":"Ann Neurol."},{"key":"B82","doi-asserted-by":"publisher","first-page":"90","DOI":"10.1093\/aje\/kwm260","article-title":"Peripheral inflammatory biomarkers and risk of Parkinson's disease","volume":"167","author":"Chen","year":"2008","journal-title":"Am J Epidemiol."},{"key":"B83","doi-asserted-by":"publisher","first-page":"6104054","DOI":"10.1155\/2017\/6104054","article-title":"IL-10: A multifunctional cytokine in viral infections","volume":"2017","author":"Rojas","year":"2017","journal-title":"J Immunol Res."},{"key":"B84","doi-asserted-by":"publisher","first-page":"6822","DOI":"10.1128\/JVI.00510-11","article-title":"Virally expressed interleukin-10 ameliorates acute encephalomyelitis and chronic demyelination in coronavirus-infected mice","volume":"85","author":"Trandem","year":"2011","journal-title":"J Virol"},{"key":"B85","doi-asserted-by":"publisher","first-page":"277","DOI":"10.1038\/nm.1929","article-title":"Effector T cells control lung inflammation during acute influenza virus infection by producing IL-10","volume":"15","author":"Sun","year":"2009","journal-title":"Nat Med."},{"key":"B86","doi-asserted-by":"publisher","first-page":"225","DOI":"10.1016\/j.virol.2010.05.004","article-title":"IFNgamma-producing, virus-specific CD8+ effector cells acquire the ability to produce IL-10 as a result of entry into the infected lung environment","volume":"404","author":"Palmer","year":"2010","journal-title":"Virology."},{"key":"B87","doi-asserted-by":"publisher","first-page":"3642","DOI":"10.4049\/jimmunol.1003292","article-title":"Highly activated cytotoxic CD8 T cells express protective IL-10 at the peak of coronavirus-induced encephalitis","volume":"186","author":"Trandem","year":"2011","journal-title":"J Immunol"},{"key":"B88","doi-asserted-by":"publisher","first-page":"209","DOI":"10.1016\/j.immuni.2009.05.012","article-title":"Interleukin-10 production by Th1 cells requires interleukin-12-induced STAT4 transcription factor and ERK MAP kinase activation by high antigen dose","volume":"31","author":"Saraiva","year":"2009","journal-title":"Immunity."},{"key":"B89","doi-asserted-by":"publisher","first-page":"1398","DOI":"10.1016\/j.jid.2015.11.034","article-title":"Cross-regulation of proinflammatory cytokines by interleukin-10 and miR-155 in orientia tsutsugamushi-infected human macrophages prevents cytokine storm","volume":"136","author":"Tsai","year":"2016","journal-title":"J Invest Dermatol."},{"key":"B90","doi-asserted-by":"publisher","first-page":"885","DOI":"10.1038\/nature01326","article-title":"The immunopathogenesis of sepsis","volume":"420","author":"Cohen","year":"2002","journal-title":"Nature."},{"key":"B91","doi-asserted-by":"publisher","first-page":"16","DOI":"10.1128\/MMBR.05015-11","article-title":"Into the eye of the cytokine storm","volume":"76","author":"Tisoncik","year":"2012","journal-title":"Microbiol Mol Biol Rev."},{"key":"B92","doi-asserted-by":"publisher","first-page":"1175","DOI":"10.1007\/s00134-006-0204-8","article-title":"Persisting low monocyte human leukocyte antigen-DR expression predicts mortality in septic shock","volume":"32","author":"Monneret","year":"2006","journal-title":"Intensive Care Med."},{"key":"B93","doi-asserted-by":"publisher","first-page":"762","DOI":"10.3390\/v11080762","article-title":"Viruses and autoimmunity: a review on the potential interaction and molecular mechanisms","volume":"11","author":"Smatti","year":"2019","journal-title":"Viruses."},{"key":"B94","doi-asserted-by":"publisher","first-page":"102301","DOI":"10.1016\/j.jaut.2019.06.012","article-title":"Bystander activation and autoimmunity","volume":"103","author":"Pacheco","year":"2019","journal-title":"J Autoimmun."},{"key":"B95","doi-asserted-by":"publisher","first-page":"102524","DOI":"10.1016\/j.autrev.2020.102524","article-title":"Could Sars-coronavirus-2 trigger autoimmune and\/or autoinflammatory mechanisms in genetically predisposed subjects?","volume":"19","author":"Caso","year":"2020","journal-title":"Autoimmun Rev."},{"key":"B96","doi-asserted-by":"publisher","first-page":"155","DOI":"10.1097\/BOR.0000000000000776","article-title":"COVID-19 and autoimmune diseases","volume":"33","author":"Liu","year":"2021","journal-title":"Curr Opin Rheumatol."},{"key":"B97","doi-asserted-by":"publisher","first-page":"3171","DOI":"10.1007\/s10067-020-05359-y","article-title":"High levels of anti-SSA\/Ro antibodies in COVID-19 patients with severe respiratory failure: a case-based review","volume":"39","author":"Fujii","year":"2020","journal-title":"Clin Rheumatol"},{"key":"B98","doi-asserted-by":"publisher","DOI":"10.21203\/rs.3.rs-254837\/v1","author":"Yumuk","year":"2021","journal-title":"Antinuclear Antibodies (ANA) in COVID-19 Infection"},{"key":"B99","doi-asserted-by":"publisher","first-page":"3621","DOI":"10.12998\/wjcc.v8.i17.3621","article-title":"Autoimmunity as the comet tail of COVID-19 pandemic","volume":"8","author":"Talotta","year":"2020","journal-title":"World J Clin Cases."},{"key":"B100","doi-asserted-by":"publisher","DOI":"10.1136\/annrheumdis-2021-219859.","article-title":"Onset of rheumatoid arthritis after COVID-19: coincidence or connected?","author":"Derksen","year":"2021","journal-title":"Ann Rheum Dis."},{"key":"B101","doi-asserted-by":"publisher","first-page":"5295","DOI":"10.3390\/ijms21155295","article-title":"The functional roles and applications of immunoglobulins in neurodegenerative disease","volume":"21","author":"Sim","year":"2020","journal-title":"Int J Mol Sci."},{"key":"B102","doi-asserted-by":"publisher","first-page":"479","DOI":"10.1007\/s00401-012-0995-3","article-title":"Intracerebral immune complex formation induces inflammation in the brain that depends on Fc receptor interaction","volume":"124","author":"Teeling","year":"2012","journal-title":"Acta Neuropathol."},{"key":"B103","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1186\/s12967-019-02175-0","article-title":"Lupus serum IgG induces microglia activation through Fc fragment dependent way and modulated by B-cell activating factor","volume":"17","author":"Yang","year":"2019","journal-title":"J Transl Med."},{"key":"B104","doi-asserted-by":"publisher","first-page":"83","DOI":"10.1080\/07853890.2017.1412088","article-title":"Autoimmune rheumatic diseases and the risk of Parkinson disease: a nationwide population-based cohort study in Taiwan","volume":"50","author":"Chang","year":"2018","journal-title":"Ann Med."},{"key":"B105","doi-asserted-by":"publisher","first-page":"1900","DOI":"10.12688\/f1000research.21140.1","article-title":"Putative autoantibodies in the cerebrospinal fluid of Alzheimer's disease patients","volume":"8","author":"Lim","year":"2019","journal-title":"F1000Res"},{"key":"B106","doi-asserted-by":"publisher","first-page":"1005","DOI":"10.1016\/j.autrev.2016.07.022","article-title":"Parkinson's disease: autoimmunity and neuroinflammation","volume":"15","author":"De Virgilio","year":"2016","journal-title":"Autoimmun Rev."},{"key":"B107","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/j.jaut.2016.10.006","article-title":"Influenza virus infection exacerbates experimental autoimmune encephalomyelitis disease by promoting type IT cells infiltration into central nervous system","volume":"77","author":"Chen","year":"2017","journal-title":"J Autoimmun."},{"key":"B108","doi-asserted-by":"publisher","first-page":"1351","DOI":"10.1007\/s10072-020-04449-8","article-title":"Early Guillain-Barr\u00e9 syndrome in coronavirus disease 2019 (COVID-19): a case report from an Italian COVID-hospital","volume":"41","author":"Ottaviani","year":"2020","journal-title":"Neurol Sci."},{"key":"B109","doi-asserted-by":"publisher","first-page":"383","DOI":"10.1016\/S1474-4422(20)30109-5","article-title":"Guillain-Barr\u00e9 syndrome associated with SARS-CoV-2 infection: causality or coincidence?","volume":"19","author":"Zhao","year":"2020","journal-title":"Lancet Neurol."},{"key":"B110","doi-asserted-by":"publisher","first-page":"1214","DOI":"10.1016\/S0140-6736(21)00517-1","article-title":"Guillain-Barr\u00e9 syndrome","volume":"397","author":"Shahrizaila","year":"2021","journal-title":"Lancet"},{"key":"B111","doi-asserted-by":"publisher","first-page":"675","DOI":"10.1080\/14737175.2021.1927713","article-title":"Pathogenesis, diagnosis and treatment of paraneoplastic neurologic syndromes","volume":"21","author":"Blaes","year":"2021","journal-title":"Expert Rev Neurother"},{"key":"B112","doi-asserted-by":"publisher","first-page":"177","DOI":"10.1097\/YCO.0000000000000688","article-title":"Coronavirus disease 2019 and neurodegenerative disease: what will the future bring?","volume":"34","author":"Mcalpine","year":"2021","journal-title":"Curr Opin Psychiatry."},{"key":"B113","doi-asserted-by":"publisher","first-page":"1061","DOI":"10.1001\/jama.2020.1585","article-title":"Clinical characteristics of 138 hospitalized patients with 2019 novel coronavirus\u2013infected pneumonia in Wuhan, China","volume":"323","author":"Wang","year":"2020","journal-title":"JAMA."},{"key":"B114","doi-asserted-by":"publisher","first-page":"762","DOI":"10.1007\/s00415-020-10123-y","article-title":"Neurological comorbidity and severity of COVID-19","volume":"268","author":"Romagnolo","year":"2021","journal-title":"J Neurol."},{"key":"B115","doi-asserted-by":"publisher","first-page":"345","DOI":"10.3390\/brainsci10060345","article-title":"COVID-19 immunopathology and the central nervous system: Implication for multiple sclerosis and other autoimmune diseases with associated demyelination","volume":"10","author":"Boziki","year":"2020","journal-title":"Brain Sci."},{"key":"B116","doi-asserted-by":"publisher","first-page":"1567","DOI":"10.1007\/s00415-020-09822-3","article-title":"Multiple sclerosis and the risk of infection: considerations in the threat of the novel coronavirus, COVID-19\/SARS-CoV-2","volume":"267","author":"Willis","year":"2020","journal-title":"J Neurol."},{"key":"B117","doi-asserted-by":"publisher","first-page":"458","DOI":"10.1016\/j.mehy.2004.08.024","article-title":"Add Alzheimer's disease to the list of autoimmune diseases","volume":"64","author":"D'andrea","year":"2005","journal-title":"Med Hypotheses."},{"key":"B118","doi-asserted-by":"publisher","first-page":"84","DOI":"10.18433\/jpps31455","article-title":"Epithelial and endothelial expressions of ACE2: SARS-CoV-2 entry routes","volume":"24","author":"Guney","year":"2021","journal-title":"J Pharmacy Pharm Sci."},{"key":"B119","doi-asserted-by":"publisher","first-page":"1895","DOI":"10.1161\/STROKEAHA.120.032711","article-title":"Endothelial dysfunction in the brain: setting the stage for stroke and other cerebrovascular complications of COVID-19","volume":"52","author":"Sashindranath","year":"2021","journal-title":"Stroke."},{"key":"B120","doi-asserted-by":"publisher","first-page":"103960","DOI":"10.1016\/j.compbiomed.2020.103960","article-title":"COVID-19 pathways for brain and heart injury in comorbidity patients: a role of medical imaging and artificial intelligence-based COVID severity classification: a review","volume":"124","author":"Suri","year":"2020","journal-title":"Comput Biol Med."},{"key":"B121","doi-asserted-by":"publisher","first-page":"1845","DOI":"10.1002\/jmv.26105","article-title":"Potential neuroinvasive pathways of SARS-CoV-2: deciphering the spectrum of neurological deficit seen in coronavirus disease-2019 (COVID-19)","volume":"92","author":"Baig","year":"2020","journal-title":"J Med Virol"},{"key":"B122","doi-asserted-by":"publisher","first-page":"1701","DOI":"10.1021\/acschemneuro.0c00286","article-title":"Heralding healthcare professionals: recognition of neurological deficits in COVID-19","volume":"11","author":"Baig","year":"2020","journal-title":"ACS Chem Neurosci"},{"key":"B123","doi-asserted-by":"publisher","first-page":"64","DOI":"10.4103\/jtccm.jtccm_5_20","article-title":"D vitamin, coronavirus, neurological injuries","volume":"2","author":"Perdomo","year":"2020","journal-title":"J Transl Crit Care Med."},{"key":"B124","doi-asserted-by":"publisher","first-page":"fcab118","DOI":"10.1093\/braincomms\/fcab118","article-title":"Gut-brain axis in the neurological comorbidity of COVID-19","volume":"3","author":"Chen","year":"2021","journal-title":"Brain Commun"}],"container-title":["Frontiers in Neurology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fneur.2021.697079\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,7,30]],"date-time":"2021-07-30T06:02:31Z","timestamp":1627624951000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fneur.2021.697079\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,7,30]]},"references-count":124,"alternative-id":["10.3389\/fneur.2021.697079"],"URL":"https:\/\/doi.org\/10.3389\/fneur.2021.697079","relation":{},"ISSN":["1664-2295"],"issn-type":[{"value":"1664-2295","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,7,30]]},"article-number":"697079"}}